Background It is often difficult to administer extended antibiotic therapy in the hospital for right-sided Staphylococcus aureus endocarditis. Although the effectiveness of single-drug therapy given for 4 to 6 weeks and that of two-drug therapy given for 2 weeks have been shown, no data are available on the effectiveness of short-course single-drug therapy. Objective To compare the efficacy of cloxacillin alone with that of cloxacillin plus gentamicin for the 2-week treatment of right-sided S. aureus endocarditis in intravenous drug users. Design Open, randomized study. Setting An academic tertiary care hospital in Barcelona, Spain. Patients 90 consecutive intravenous drug users who had isolated tricuspid valve endocarditis caused by methicillin-susceptible S. aureus, had no allergy to study medications, and had no systemic infectious complications that required prolonged therapy. An efficacy subset consisted of 74 of these patients who did not meet an exclusion criterion. Intervention Cloxacillin (2 g intravenously every 4 hours for 14 days) alone or combined with gentamicin (1 mg/kg of body weight intravenously every 8 hours for 7 days). Measurements Clinical or microbiological evidence of active infection after 2 weeks of therapy, relapse of staphylococcal infection, or death. Results In an analysis of the efficacy subset, treatment was successful in 34 of the 38 patients who received cloxacillin alone (89% [95% CI, 75% to 97%]) and 31 of the 36 patients who received cloxacillin plus gentamicin (86% [CI, 71% to 95%]). Three patients died: one in the cloxacillin group and two in the combination therapy group. Of the 37 patients who completed 2-week treatment with cloxacillin, 34 (92%) were cured, and 3 (8%) needed prolonged treatment to cure the infection. Of the 34 patients who completed 2-week treatment with cloxacillin plus gentamicin, 32 (94%) were cured and 2 (6%) required treatment for 4 weeks. One patient in the combination group had relapse. Conclusions A penicillinase-resistant penicillin used as single-agent therapy for 2 weeks was effective for most patients with isolated tricuspid endocarditis caused by methicillin-susceptible S. aureus. Adding gentamicin did not appear to provide any therapeutic advantages. Additional studies to confirm the therapeutic equivalence of short-course therapy with penicillinase-resistant penicillin alone and therapy with combined regimens are warranted.

Effectiveness of Cloxacillin with and without Gentamicin in Short-Term Therapy for Right-Sided Staphylococcus aureus Endocarditis: A Randomized, Controlled Trial

Background The addition of an aminoglycoside to a beta-lactam for the treatment of patients with infective endocarditis has been supported by data from laboratory and animal studies. Purpose We sought to review the evidence from the available comparative clinical trials regarding the role of aminoglycosides in combination with a beta-lactam for the treatment of bacterial endocarditis caused by Gram-positive cocci. Data sources The studies for our meta-analysis were retrieved from searches of the PubMed and Cochrane Central Register of Controlled Trials databases, as well as from the references cited in relevant articles. No limits were set regarding the language and date of publication of the studies. Study selection Included studies were prospective studies that provided comparative data regarding the effectiveness of the treatment and/or mortality in patients receiving monotherapy with a beta-lactam or beta-lactam/aminoglycoside combination therapy. Data extraction Two independent reviewers performed the literature search, study selection and extraction of data from relevant studies. Data synthesis No clinical trial comparing beta-lactam monotherapy with beta-lactam/aminoglycoside combination therapy for the treatment of enterococcal endocarditis was found. We performed a meta-analysis of five available comparative trials [four randomized controlled trials (RCTs) and one comparative prospective trial], which included 261 patients with bacterial endocarditis in native valves due to Staphylococcus aureus (four studies) or streptococci of the viridans group (one study). There was no statistically significant difference between beta-lactam monotherapy and beta-lactam/aminoglycoside combination therapy regarding mortality [odds ratio (OR) = 0.59, 95% confidence interval (95% CI) = 0.21-1.66], treatment success (OR = 1.25, 95% CI = 0.49-3.05), treatment success without surgery (OR = 1.66, 95% CI = 0.64-4.30) or relapse of endocarditis (OR = 0.79, 95% CI = 0.15-4.29). Nephrotoxicity was less common in the beta-lactam monotherapy arm than in the beta-lactam/aminoglycoside combination therapy arm (OR = 0.38, 95% CI = 0.16-0.88, P = 0.024). No difference between the two treatment arms was found in subanalyses of the four studies that included only patients with staphylococcal infections in terms of mortality (OR = 0.69, 95% CI = 0.26-1.86, fixed effects model), treatment success (OR = 1.27, 95% CI = 0.47-3.43, fixed effects model) or relapse (OR = 0.76, 95% CI = 0.12-4.92, fixed effects model). Limitations The relatively small number of available comparative trials was the major limitation of this meta-analysis. Conclusions The limited evidence from the available prospective comparative studies does not offer support for the addition of an aminoglycoside to beta-lactam treatment of patients with endocarditis caused by Gram-positive cocci. A large multicentre RCT is necessary to reach a definitive conclusion on this issue.

/pdf/the-role-of-aminoglycosides-in-combination-with-a-b-lactam-4nrgsn61j0.pdf

The role of aminoglycosides in combination with a β-lactam for the treatment of bacterial endocarditis: a meta-analysis of comparative trials

https://www.cardiology.theclinics.com/article/S0733-8651(03)00025-0/pdf

Infective endocarditis and cardiac surgery in intravenous drug abusers and HIV-1 infected patients.

Right-sided endocarditis caused by Staphylococcus aureus is a frequent complication of injection drug use. Fortunately, the prognosis for this infection when treated with the standard regimen of 4 to 6 weeks of parenteral antistaphylococcal antibiotics is favorable. Nevertheless, in many cases, once drug users feel better, they leave the hospital against medical advice before completing the full course of antibiotic therapy. This problem has stimulated interest in shortening the duration of antibiotic to a penicillinase-resistant penicillin. Data from in vitro synergy studies and animal models of endocarditis suggest that S. aureus can be eradicated more quickly by combination therapy than by monotherapy. Reports of three prospective, nonrandomized clinical trials have been published that support the use of a 2-week course of a penicillinase-resistant penicillin and an aminoglycoside antibiotic to treat uncomplicated, exclusively right-sided endocarditis caused by methicillin-susceptible S. aureus in injection drug users.

Short-course antibiotic therapy for right-sided endocarditis caused by Staphylococcus aureus in injection drug users.

Infective endocarditis (IE) is one of the most severe complications in intravenous drug abusers (IVDA). IE usually involves the tricuspid valve, Staphylococcus aureus is the most common etiologic agent, and it has a relatively good prognosis. Currently, between 40% and 90% of IVDA with IE are HIV infected, and the HIV epidemic has caused a decrease in the incidence of this disease, probably due to changes in drug administration habits undertaken by addicts in order to avoid HIV transmission. This review focuses on progress made over the past few years in some aspects of IE in IVDA. The pathogenesis of tricuspid endocarditis is still unknown more than 60 years after the first series. The most important advance in antibiotic therapy is that noncomplicated S. aureus right-sided endocarditis can be successfully treated with an intravenous 2-week course of nafcillin or cloxacillin plus an aminoglycoside, although probably the aminoglycoside administration could be stopped after the first 3 to 5 days. Surgery in HIV-infected IVDA with IE does not worsen the prognosis. Considering the possibility of reinfection in IVDA, prosthetic material is usually avoided. Tricuspid valvulectomy or valve repair should be considered the technique of choice in IVDA with right-sided IE. Replacement of the tricuspid valve by a cryopreserved mitral homograft is the latest introduction into clinical practice. It provides atrioventricular competence, thereby avoiding late right heart failure. Reinfections can be treated medically with a negligible reoperation rate. Overall mortality for HIV-infected or non-HIV-infected IVDA with IE is similar. However, among HIV-infected IVDA, mortality is significantly higher in those who are most severely immunosuppressed, with CD4(+) cell counts below 200/L or with AIDS criteria.

https://link.springer.com/content/pdf/10.1007/s11908-003-0007-9.pdf

Infective Endocarditis in Intravenous Drug Abusers.

Background Intravenous drug addicts (IVDA) are a group of patients in whom it is difficult to complete standard treatment of infectious endocarditis due to frequent antisocial behavior and in whom, once clinical improvement is achieved, voluntary discharge is frequently requested. This is why the evaluation of new treatment schedules tending to decrease the length of the same is of great interest. This non randomized study has the aim of knowing the efficacy of a short treatment with cloxacillin or vancomycin associated to gentamicin in right-sided endocarditis by methicillin-sensitive Staphylococcus aureus, comparing this with the standard schedule of 28 days. Methods This series was made up of IVDA patients diagnosed of right endocarditis by S. aureus. Inclusion criteria were the presence of intravenous drug addiction, isolation of methicillin-sensitive S. aureus in 2 or more blood cultures and achievement of the diagnostic criteria of right-sided endocarditis. Two schedules were used: a) standard: cloxacillin or vancomycin for 4 weeks, associating aminoglucoside in the first 3-5 days; b) short; cloxacillin or vancomycin associated to gentamicin for 2 weeks with no ulterior treatment. The study was not randomized and the treatment of 2 weeks was compared with historic controls treated for 4 weeks. The criteria evaluated were those of clinical cure, relapse, appearance of complications during treatment and mortality. Results Both the standard treatment and the combination of cloxacillin or vancomycin with gentamicin for 2 weeks cured 100% of the episodes of right endocarditis by S. aureus. There were no relapses and mortality was nul. Neither were there any differences between the two groups with regard to appearance of complications. Conclusions In intravenous drug addict patients with right-sided endocarditis by methicillin S. aureus, the association of cloxacillin and gentamicin for 2 weeks is an effective alternative to long (4 week) treatments with only one antibiotic. The low number of cases treated with vancomycin does not allow conclusions to be drawn on its efficacy.

[Right endocarditis caused by Staphylococcus aureus in parenteral drug addicts: evaluation of a combined therapeutic scheme for 2 weeks versus conventional treatment].

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[Right endocarditis caused by Staphylococcus aureus in parenteral drug addicts: evaluation of a combined therapeutic scheme for 2 weeks versus conventional treatment].